Program 3. Discovery and Developmental Therapeutics (DDT): The overall scientific goal of the Cancer Discovery and Developmental Therapeutics (DDT) Program is to enhance the discovery of new agents and advance their translation into the prevention and treatment of patients with cancer. The program has two full specific aims, and two major developing aims. The overall goal is to foster a highly collaborative team science environment, building on the existing strong ties with the MPB, CGE and CCPS Programs, to promote molecular target-based cancer drug discovery and to facilitate translational clinical trials for effective therapeutic development. To achieve this goal, the Program is organized with the following foci: (1) To identify small molecule modulators of tumor-addicted signaling pathways for cancer drug discovery; (2) To carry out mechanism-driven clinical trials for cancer drug development to rapidly move new agents to patients; (3) To translate discoveries in cancer immunology into mechanistically driven clinical trials enhancing the therapy of patients with hematologic malignancies and immuno-responsive solid tumors; (4) To test promising agents early in their life cycle in the multi-modality setting using mechanism-based clinical trials in conjunction with optimized chemo-radiation, radiation or surgery. We plan to achieve the goal of developing novel therapeutic approaches to the prevention and treatment of cancer through close intra- and inter-programmatic interactions by focusing on such areas as: (1) chemoprevention, (2) molecularly-targeted therapy, (3) new drug discovery, (4) biological interaction between epithelial and surrounding tissue, (5) nanotherapeutics, (6) cancer immunotherapy, (7) biomedical research platforms using innovative technology to prevent and treat tumors, and (8) translational multimodality research for advanced solid malignancies. The DDT Program comprises a diverse group of 45 members from 15 different departments within the School of Medicine, the School of Public Health and Emory College. The DDT Program has total peerreviewed program funding of $23 M, of which NCI funding represents $17.5M ($13.6M direct). In addition, there is a total of $1.9 M in non-peer-reviewed support from various sources. Program members have published a total of 535 papers during the last five years, of which 47% are intra-programmatic and 53% are inter-programmatic.